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780 TABLE I-DEATHS OF 12 g. BALB/C MICE AFTER INTRAVENOUS INJECTION OF DIFFERENT DOSES OF ADSORBED AND UNADSORBED CYSTAMINE AND OF INDIAN INK* None of 10 mice died after injection with an amount of indian ink equal to that used for adsorption. t Numerator = number of dead mice; denominator = number of mice in group. are well known to possess some protective effect in irradiation. 6 However, toxicity for the central nervous system prevents the use of these substances in large doses. We therefore studied toxicity and protective effect of cystamine in aqueous solution and adsorbed on indian ink. Female mice of BALB/c strain weighing 12-24 g. were used. Chromatography on filter-paper, using the nitroprusside test, showed that cystamine adsorption was complete at pH 7-0, with a cystamine/indian-ink ratio of 1/6. Cystamine adsorbed on powdered charcoal, in 1/6 ratio, was therefore used for oral administration. Mice were irradiated in RUM-11 ’ apparatus with voltage 200 kV, current intensity 15 milliamps, and filter of 0-5 mm. diameter copper and 1 mm. diameter aluminium wires; skin-focus distance was 50 cm.; and power was 20r per minute. Table I shows that twice as much cystamine adsorbed on indian ink as cystamine in aqueous solution may be injected TABLE II-PROTECTIVE EFFECT OF 150 mg. per kg. OF CYSTAMINE IN 24 g. BALB/C MICE IRRADIATED WITH 800r .. Numerator = number of dead animals; denominator=number of animals in group. t Severe lesions of intestines found at necropsy. into mice intravenously without toxic manifestations. Aqueous solution of cystamine in a dose of 150 mg. per kg. caused immediate convulsions and death of mice. Therefore in our irradiation experiments this dose of unadsorbed cystamine in aqueous solution had to be injected intraperitoneally. In another experiment we compared the protective effect of 150 mg. per kg. of cystamine in aqueous solution and when adsorbed, inoculated 15-20 minutes before irradiation of the mice with 800r. Table II shows the good protective effect of indian-ink-adsorbed cystamine. In the last experiment we compared the effect of the same doses of unadsorbed and adsorbed cystamine given intra- venously (50 mg. per kg.) and per os (100 mg. per kg.). Each group of 10 mice were irradiated with 560r 2 hours after administration of the protective substance. By the 10th day of observation all mice receiving adsorbed cystamine were alive without any abnormal signs. Mice receiving aqueous solution of cystamine had loose stools, sickened, and died, beginning at 7 days, with symptoms of radiation disease; only 2 of the 10 mice in this group had survived for 10 days (table ill). 6. Semenov, L. F., Prokudina, E. A. Problems of Radiobiology; vol. II, p. 394. Leningrad, 1957. Doherty, D., Burnett, W., Shapiro, R. Radiat. Res. 1957, 7, 13. TABLE III-PROTECTIVE EFFECT OF 150 mg. per kg. OF CYSTAMINE (50 mg. per kg. INTRAVENOUSLY AND 100 mg. per kg. per os) IN 14 g. BAL]3/C MICE IRRADIATED WITH 560r * Numerator = number of animals dead; denominator =number of animals in group. Our method of protection thus permits the use of known radioprotective substances adsorbed on or chemically combined with different corpuscular and macromolecular carriers, as well as suggesting the creation of new radioprotective compounds with large (macro) molecules. G. J. SVET-MOLDAVSKY A. I. PAVLOTSKY. Laboratory of Virology, Institute of Experimental and Clinical Oncology, Kashirskoe Shosse 6, Moscow M-478. CHRISTMAS GIFTS FUND SIR,-I should be grateful if you would once more allow me to make known in your columns the Christmas Gifts appeal that is made annually by the Royal Medical Benevolent Fund. This special gifts fund is distributed to the hundreds of beneficiaries at Christmas-tide, when the little extra makes such a welcome increase to their happiness. We feel sure that the profession will make a generous response to this appeal. Contributions, marked " Christmas Gifts ", should be sent to the Royal Medical Benevolent Fund, 24 King’s Road, Wimbledon, London S.W.19. ZACHARY COPE President, Royal Medical Benevolent Fund. Public Health Smallpox Vaccination THE Ministry of Health has issued a revised memorandum of advice on how to administer smallpox vaccine. Liquid vaccine, stained with brilliant-green, is now supplied in plastic tubing. The contraindications for routine primary vaccination differ from those given in the 1962 edition of this memorandum. They are: septic skin conditions, history of eczema or other allergic conditions, hypoganunaglobulinxmia, leukaemia, and corticosteroid and immunosuppressive treatment; to these should be added failure to thrive and exposure to infectious diseases in early childhood, and, in later life, pregnancy. In cases of exposure to smallpox, antivaccinial gamma-globulin (obtainable from public-health laboratories) should be given in the opposite arm when vaccinating contacts who are pregnant, who have eczema (or definite history of the disease), leukaemia, or hypogammaglobulinaemia, or who are being treated with corticosteroids or immunosuppressive therapy. The vaccina- tion site should be inspected on or about the seventh day (the third day in cases of exposure), and the nature of the reaction- (a) major, (b) equivocal, or (c) no local reaction-should be noted. " Vaccinators " are reminded that the procedure is not obligatory for travellers if a medical contraindication exists: under these circumstances a written opinion to this effect should be supplied. 1. Memorandum on Vaccination Against Smallpox. H.M. Stationery Office, 1967. Pp. 11. 1s. 6d.

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780

TABLE I-DEATHS OF 12 g. BALB/C MICE AFTER INTRAVENOUS INJECTIONOF DIFFERENT DOSES OF ADSORBED AND UNADSORBED CYSTAMINE AND

OF INDIAN INK*

None of 10 mice died after injection with an amount of indian ink equalto that used for adsorption.

t Numerator = number of dead mice; denominator = number of mice ingroup.

are well known to possess some protective effect in irradiation. 6However, toxicity for the central nervous system prevents theuse of these substances in large doses. We therefore studiedtoxicity and protective effect of cystamine in aqueous solutionand adsorbed on indian ink. Female mice of BALB/c strainweighing 12-24 g. were used. Chromatography on filter-paper,using the nitroprusside test, showed that cystamine adsorptionwas complete at pH 7-0, with a cystamine/indian-ink ratio of1/6. Cystamine adsorbed on powdered charcoal, in 1/6 ratio,was therefore used for oral administration. Mice were

irradiated in RUM-11 ’ apparatus with voltage 200 kV,current intensity 15 milliamps, and filter of 0-5 mm. diametercopper and 1 mm. diameter aluminium wires; skin-focusdistance was 50 cm.; and power was 20r per minute.

Table I shows that twice as much cystamine adsorbed onindian ink as cystamine in aqueous solution may be injected

TABLE II-PROTECTIVE EFFECT OF 150 mg. per kg. OF CYSTAMINE IN24 g. BALB/C MICE IRRADIATED WITH 800r

.. Numerator = number of dead animals; denominator=number of animalsin group.

t Severe lesions of intestines found at necropsy.

into mice intravenously without toxic manifestations. Aqueoussolution of cystamine in a dose of 150 mg. per kg. causedimmediate convulsions and death of mice. Therefore in ourirradiation experiments this dose of unadsorbed cystamine inaqueous solution had to be injected intraperitoneally. Inanother experiment we compared the protective effect of150 mg. per kg. of cystamine in aqueous solution and whenadsorbed, inoculated 15-20 minutes before irradiation of themice with 800r. Table II shows the good protective effect ofindian-ink-adsorbed cystamine.

In the last experiment we compared the effect of the samedoses of unadsorbed and adsorbed cystamine given intra-

venously (50 mg. per kg.) and per os (100 mg. per kg.). Eachgroup of 10 mice were irradiated with 560r 2 hours afteradministration of the protective substance. By the 10th day ofobservation all mice receiving adsorbed cystamine were alivewithout any abnormal signs. Mice receiving aqueous solutionof cystamine had loose stools, sickened, and died, beginning at7 days, with symptoms of radiation disease; only 2 of the 10mice in this group had survived for 10 days (table ill).6. Semenov, L. F., Prokudina, E. A. Problems of Radiobiology; vol. II,

p. 394. Leningrad, 1957. Doherty, D., Burnett, W., Shapiro, R.Radiat. Res. 1957, 7, 13.

TABLE III-PROTECTIVE EFFECT OF 150 mg. per kg. OF CYSTAMINE(50 mg. per kg. INTRAVENOUSLY AND 100 mg. per kg. per os) IN14 g. BAL]3/C MICE IRRADIATED WITH 560r

* Numerator = number of animals dead; denominator =number of animalsin group.

Our method of protection thus permits the use of knownradioprotective substances adsorbed on or chemically combinedwith different corpuscular and macromolecular carriers, as wellas suggesting the creation of new radioprotective compoundswith large (macro) molecules.

G. J. SVET-MOLDAVSKYA. I. PAVLOTSKY.

Laboratory of Virology,Institute of Experimental and

Clinical Oncology,Kashirskoe Shosse 6,Moscow M-478.

CHRISTMAS GIFTS FUND

SIR,-I should be grateful if you would once more allow meto make known in your columns the Christmas Gifts appealthat is made annually by the Royal Medical Benevolent Fund.This special gifts fund is distributed to the hundreds ofbeneficiaries at Christmas-tide, when the little extra makessuch a welcome increase to their happiness. We feel sure thatthe profession will make a generous response to this appeal.

Contributions, marked " Christmas Gifts ", should be sentto the Royal Medical Benevolent Fund, 24 King’s Road,Wimbledon, London S.W.19.

ZACHARY COPEPresident,

Royal Medical Benevolent Fund.

Public Health

Smallpox VaccinationTHE Ministry of Health has issued a revised memorandum

of advice on how to administer smallpox vaccine. Liquidvaccine, stained with brilliant-green, is now supplied in plastictubing. The contraindications for routine primary vaccinationdiffer from those given in the 1962 edition of this memorandum.They are: septic skin conditions, history of eczema or otherallergic conditions, hypoganunaglobulinxmia, leukaemia, andcorticosteroid and immunosuppressive treatment; to theseshould be added failure to thrive and exposure to infectiousdiseases in early childhood, and, in later life, pregnancy. Incases of exposure to smallpox, antivaccinial gamma-globulin(obtainable from public-health laboratories) should be given inthe opposite arm when vaccinating contacts who are pregnant,who have eczema (or definite history of the disease), leukaemia,or hypogammaglobulinaemia, or who are being treated withcorticosteroids or immunosuppressive therapy. The vaccina-tion site should be inspected on or about the seventh day (thethird day in cases of exposure), and the nature of the reaction-(a) major, (b) equivocal, or (c) no local reaction-should benoted. " Vaccinators " are reminded that the procedure is notobligatory for travellers if a medical contraindication exists:under these circumstances a written opinion to this effect shouldbe supplied.1. Memorandum on Vaccination Against Smallpox. H.M. Stationery

Office, 1967. Pp. 11. 1s. 6d.